This invention is directed to designs and methods for delivering and infusing dosage forms containing riboflavin or photosensitizer analogues, or other ophthalmic formulations, into ocular tissue (such as equatorial and posterior sclera tissue). The riboflavin is then activated by delivering UVA irradiation onto the tissue which facilitates effective rigidity by cross-linking of collagen molecules therein.
Collagen cross-linking (CXL) in the cornea is now a widespread method used to stiffen and stabilize corneal tissue for the treatment of keratoconus, a degenerative collagenous disease. CXL has been shown to prevent the progression of keratonconus by collagen stiffening. There are other conditions and diseases of the cornea where CXL treatment has been shown to be safe and effective, for example: corneal ectasia, corneal ulceration, infective keratitis, and bullous keratopathy. Importantly, recent animal studies have shown that CXL has the same stabilizing effect on degenerative sclera tissue as it does on corneal tissue.
Progressive myopia primarily manifests in the pre-teen years due to unknown causes. The primary characteristics of this condition include the elongation of both eyes (i.e. the axial length of each eyeball progressively extends beyond 24 mm to over 26 mm) and greater than −6 diopters of ametropia. The stretching of the eye occurs over a period of years, usually beginning in early childhood (3 years old) and continuing until adulthood (18 years old). This stretching is accompanied by regional thinning of the sclera, primarily in the equator and posterior regions.
FIG. 1 compares a normal eye to a progressive myopic eye. The sclera covers the eyeball, except for the cornea, and the sclera's dense collagen fiber controls the size of the eye. As shown in FIG. 1, with a progressive myopic eye the scleral tissue has become stretched and thereby creates a mismatch between the eye's normal focal point and the axial length of the eye. A person with this condition becomes severely nearsighted (>−6 diopters).
Reduced visual acuities are not the only problem caused by progressive myopia. Additionally, there is an extremely high correlation (>75%) between the following serious conditions and unabated progressive myopia, which at a later age (usually >50 yrs) can induce pathologic sequelae (sometimes referred to as pathologic myopia), such as:
Retinal detachment
Choroidal Neo-Vascularization (CNV)
Lacquer cracks
Posterior Staphylomas.
Currently there is no effective treatment for progressive myopia.
The invention herein described includes methodology for cross-linking scleral tissue. Cross-linking as discussed herein is a two-step process wherein tissue rigidity and shape stability are enhanced. The first step involves the application of a photo-sensitizer such as riboflavin (Vitamin B-2), which is infused into the collagen tissue of the sclera. There are several novel methods described herein for this infusion of the photo-sensitizer such as riboflavin (herein “RIF”). After the riboflavin saturates the scleral tissue, step two is ready to be implemented. This second step involves the generation of radical oxygen species through the application of ultraviolet light (herein “UVA”) to the infused R/F in the scleral collagen tissue. Without being limited by theory, these radical oxygen species trigger the formation of covalent bonds between and within collagen strands as well as, it is hypothesized, bridging bonds between collagen fibrils and the local extracellular matrix (ECM). The result of this bonding is to impart an increase in biomechanical rigidity or stiffness to the treated ocular tissue.
Methods and apparatus to reduce, limit, and/or arrest progressive myopia through the application of novel cross-linking techniques is being proposed herein. As mentioned above, cross-linking of corneal tissue has become a standard of care in the EU, primarily for the treatment of keratoconus. However, there is a need to provide safe, rapid, and effective devices and techniques for cross-linking scleral collagen tissue with an outcome that affords patient comfort, stability, reliable uniformity and retention. Wollensak, Spoerl and Iseli are among the few researchers who have published their investigations of scleral crosslinking on enucleated porcine and in vivo rabbit eyes. Their results are promising and with only minor complications reported. However, the devices used in these studies are more suited for animal work and would not be adequate in a clinical setting. There is a need for more advanced devices which are suitable in both ophthalmological adult and pediatric surgical theaters.